Inhibiting Ca channels in Alzheimer's disease model mice relaxes pericytes, improves cerebral blood flow and reduces immune cell stalling and hypoxia.

Early in Alzheimer's disease (AD), pericytes constrict capillaries, increasing their hydraulic resistance and trapping of immune cells and, thus, decreasing cerebral blood flow (CBF). Therapeutic approaches to attenuate pericyte-mediated constriction in AD are lacking. Here, using in vivo two-photon imaging with laser Doppler and speckle flowmetry and magnetic resonance imaging, we show that Ca entry via L-type voltage-gated calcium channels (CaVs) controls the contractile tone of pericytes.

Microglial-derived C1q integrates into neuronal ribonucleoprotein complexes and impacts protein homeostasis in the aging brain.

Neuroimmune interactions mediate intercellular communication and underlie critical brain functions. Microglia, CNS-resident macrophages, modulate the brain through direct physical interactions and the secretion of molecules. One such secreted factor, the complement protein C1q, contributes to complement-mediated synapse elimination in both developmental and disease models, yet brain C1q protein levels increase significantly throughout aging.

Noradrenaline released from locus coeruleus axons contracts cerebral capillary pericytes via adrenergic receptors.

Noradrenaline (NA) release from locus coeruleus axons generates vascular contractile tone in arteriolar smooth muscle and contractile capillary pericytes. This tone allows neuronal activity to evoke vasodilation that increases local cerebral blood flow (CBF). Much of the vascular resistance within the brain is located in capillaries and locus coeruleus axons have NA release sites closer to pericytes than to arterioles.

Immune-vascular mural cell interactions: consequences for immune cell trafficking, cerebral blood flow, and the blood-brain barrier.

Brain barriers are crucial sites for cerebral energy supply, waste removal, immune cell migration, and solute exchange, all of which maintain an appropriate environment for neuronal activity. At the capillary level, where the largest area of brain-vascular interface occurs, pericytes adjust cerebral blood flow (CBF) by regulating capillary diameter and maintain the blood-brain barrier (BBB) by suppressing endothelial cell (EC) transcytosis and inducing tight junction expression between ECs. Pericytes also limit the infiltration of circulating leukocytes into the brain where resident microglia confine brain injury and provide the first line of defence against invading pathogens.

The Ca2+-gated channel TMEM16A amplifies capillary pericyte contraction and reduces cerebral blood flow after ischemia.

Pericyte-mediated capillary constriction decreases cerebral blood flow in stroke after an occluded artery is unblocked. The determinants of pericyte tone are poorly understood. We show that a small rise in cytoplasmic Ca2+ concentration ([Ca2+]i) in pericytes activated chloride efflux through the Ca2+-gated anion channel TMEM16A, thus depolarizing the cell and opening voltage-gated calcium channels.

Microbiota composition and mucosal immunity in patients with asymptomatic diverticulosis and controls.

Introduction: The etiology of diverticulosis is still poorly understood. However, in patients with diverticulitis, markers of mucosal inflammation and microbiota alterations have been found. The aim of this study was to evaluate potential differences of the gut microbiota composition and mucosal immunity between patients with asymptomatic diverticulosis and controls.

Monitoring phagocytic uptake of amyloid β into glial cell lysosomes in real time.

Phagocytosis by glial cells is essential to regulate brain function during health and disease. Therapies for Alzheimer's disease (AD) have primarily focused on targeting antibodies to amyloid β (Aβ) or inhibitng enzymes that make it, and while removal of Aβ by phagocytosis is protective early in AD it remains poorly understood. Impaired phagocytic function of glial cells during later stages of AD likely contributes to worsened disease outcome, but the underlying mechanisms of how this occurs remain unknown.

A retrospective study on incidence, diagnosis, and clinical outcome of gastric-type endocervical adenocarcinoma in a single institution.

Background: Gastric-type endocervical adenocarcinoma is rare but the most common subtype of cervical adenocarcinoma not associated with human papillomavirus. It is more aggressive with a shorter five-year survival rate compared to human papillomavirus-associated usual type endocervical adenocarcinoma. The objectives of our study were to determine the incidence and clinical-pathological characteristics of Gastric-type endocervical adenocarcinoma in a single institution.

Glucagon-like peptide-1 (GLP-1) receptor activation dilates cerebral arterioles, increases cerebral blood flow, and mediates remote (pre)conditioning neuroprotection against ischaemic stroke.

Stroke remains one of the most common causes of death and disability worldwide. Several preclinical studies demonstrated that the brain can be effectively protected against ischaemic stroke by two seemingly distinct treatments: remote ischaemic conditioning (RIC), involving cycles of ischaemia/reperfusion applied to a peripheral organ or tissue, or by systemic administration of glucagon-like-peptide-1 (GLP-1) receptor (GLP-1R) agonists. The mechanisms underlying RIC- and GLP-1-induced neuroprotection are not completely understood.

Cerebral blood flow decrease as an early pathological mechanism in Alzheimer's disease.

Therapies targeting late events in Alzheimer's disease (AD), including aggregation of amyloid beta (Aβ) and hyperphosphorylated tau, have largely failed, probably because they are given after significant neuronal damage has occurred. Biomarkers suggest that the earliest event in AD is a decrease of cerebral blood flow (CBF). This is caused by constriction of capillaries by contractile pericytes, probably evoked by oligomeric Aβ.

Amyloid β oligomers constrict human capillaries in Alzheimer's disease via signaling to pericytes.

Cerebral blood flow is reduced early in the onset of Alzheimer's disease (AD). Because most of the vascular resistance within the brain is in capillaries, this could reflect dysfunction of contractile pericytes on capillary walls. We used live and rapidly fixed biopsied human tissue to establish disease relevance, and rodent experiments to define mechanism.

Glutaric Acid Affects Pericyte Contractility and Migration: Possible Implications for GA-I Pathogenesis.

Glutaric acidemia I (GA-I) is an inherited neurometabolic childhood disease characterized by bilateral striatal neurodegeneration upon brain accumulation of millimolar concentrations of glutaric acid (GA) and related metabolites. Vascular dysfunction, including abnormal cerebral blood flow and blood-brain barrier damage, is an early pathological feature in GA-I, although the affected cellular targets and underlying mechanisms remain unknown. In the present study, we have assessed the effects of GA on capillary pericyte contractility in cerebral cortical slices and pericyte cultures, as well as on the survival, proliferation, and migration of cultured pericytes.

Quality of Life and Persistent Symptoms After Uncomplicated Acute Diverticulitis.

Background: Although acute diverticulitis and its recurrence are well studied, little is known about the period after these attacks have passed. Many patients appear to be affected by persistent symptoms that impair quality of life. The few published studies on this topic are mostly limited by the lack of CT confirmation of the acute diverticulitis diagnosis, low numbers of patients, or cross-sectional design.

Non- or Minimally Displaced Distal Radial Fractures in Adult Patients: Three Weeks versus Five Weeks of Cast Immobilization-A Randomized Controlled Trial.

 Patients with non- or minimally displaced distal radial fractures, that do not need repositioning, are mostly treated by a short-arm cast for a period of 4 to 6 weeks. A shorter period of immobilization may lead to a better functional outcome.  We conducted a randomized controlled trial to evaluate whether the duration of cast immobilization for patients with non- or minimally displaced distal radial fractures can be safely shortened toward 3 weeks.

Targeting pericytes for therapeutic approaches to neurological disorders.

Many central nervous system diseases currently lack effective treatment and are often associated with defects in microvascular function, including a failure to match the energy supplied by the blood to the energy used on neuronal computation, or a breakdown of the blood-brain barrier. Pericytes, an under-studied cell type located on capillaries, are of crucial importance in regulating diverse microvascular functions, such as angiogenesis, the blood-brain barrier, capillary blood flow and the movement of immune cells into the brain. They also form part of the "glial" scar isolating damaged parts of the CNS, and may have stem cell-like properties.

Derivation of phenotypically diverse neural culture from hESC by combining adherent and dissociation methods.

Background: Differentiation of human embryonic stem cells (hESCs) into distinct neural lineages has been widely studied. However, preparation of mixed yet neurochemically mature populations, for the study of neurological diseases involving mixed cell types has received less attention.

New Method: We combined two commonly used differentiation methods to provide robust and reproducible cultures in which a mixture of primarily GABAergic and Glutamatergic neurons was obtained.

Long-Term Effects of Omitting Antibiotics in Uncomplicated Acute Diverticulitis.

Background: Traditionally uncomplicated acute diverticulitis was routinely treated with antibiotics, although evidence for this strategy was lacking. Recently, two randomized clinical trials (AVOD trial and DIABOLO trial) published short-term results of omitting antibiotics compared to routine antibiotic treatment. Both showed no significant differences regarding recovery from the initial episode, as well as rates of complicated or recurrent diverticulitis and sigmoid resection.

Postoperative continuous-flow cryocompression therapy in the acute recovery phase of hip fracture surgery-A randomized controlled clinical trial.

Background: The acute recovery phase after hip fracture surgery is often complicated by severe pain, postoperative blood loss with subsequent transfusion, and delirium. Prevalent comorbidity in hip fracture patients limit the use of opioid-based analgesic therapies, yielding a high risk for inferior pain treatment. Postoperative cryotherapy is suggested to provide an analgesic effect, and to reduce postoperative blood loss.

Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis.

Background: Antibiotics are advised in most guidelines on acute diverticulitis, despite a lack of evidence to support their routine use. This trial compared the effectiveness of a strategy with or without antibiotics for a first episode of uncomplicated acute diverticulitis.

Methods: Patients with CT-proven, primary, left-sided, uncomplicated, acute diverticulitis were included at 22 clinical sites in the Netherlands, and assigned randomly to an observational or antibiotic treatment strategy.

Diagnosing perforated appendicitis in pediatric patients: a new model.

Objective: Studies have investigated sensitivity and specificity of symptoms and tests for diagnosing appendicitis in children. Less is known with regard to the predictive value of these symptoms and tests with respect to the severity of appendicitis. The aim of this study was to determine the predictive value of patient's characteristics and tests for discriminating between perforated and nonperforated appendicitis in children.

Hair thread tourniquet syndrome in a toe of an 18 mo old girl.

Hair thread tourniquet syndrome is rare and usually affects little children. If the tourniquet is not incised, the affected body part becomes ischemic or even necrotic. An 18 mo old girl was seen in the emergency ward with a painful, red and swollen third toe of the left foot.

Randomized controlled multicentre study comparing biological mesh closure of the pelvic floor with primary perineal wound closure after extralevator abdominoperineal resection for rectal cancer (BIOPEX-study).

Background: Primary perineal wound closure after conventional abdominoperineal resection (cAPR) for rectal cancer has been the standard of care for many years. Since the introduction of neo-adjuvant radiotherapy and the extralevator APR (eAPR), oncological outcome has been improved, but at the cost of increased rates of perineal wound healing problems and perineal hernia. This has progressively increased the use of biological meshes, although not supported by sufficient evidence.

The complicated Allen-Masters syndrome: small bowel herniation through a broad ligament defect.

Small bowel obstruction through a broad ligament defect is a very rare condition. We present 2 cases, one without any associated abdominal trauma. Rapid diagnosis and treatment of this rare condition is of paramount importance.

Fecal microbiome analysis as a diagnostic test for diverticulitis.

Disease-specific variations in intestinal microbiome composition have been found for a number of intestinal disorders, but little is known about diverticulitis. The purpose of this study was to compare the fecal microbiota of diverticulitis patients with control subjects from a general gastroenterological practice and to investigate the feasibility of predictive diagnostics based on complex microbiota data. Thirty-one patients with computed tomography (CT)-proven left-sided uncomplicated acute diverticulitis were included and compared with 25 control subjects evaluated for a range of gastrointestinal indications.